Clinical data indicate that genetic and environmental influences are involved in differentially predisposing individuals to begin, maintain, and relapse to drug-taking behaviors. The long-range goal of the proposed research is to use quantitative behavioral genetics, gene mapping techniques, and behavioral measures to identify genetic factors that influence biobehavioral responses to stress, drugs, and stress by drug interactions to determine underlying mechanisms involved in drug addiction. The objective in pursuit of this goal is to examine genetic influences on behavioral and biological responses to stress and to effects of stress on morphine self-administration. In Experiment 1, behavioral, physiological, and biological stress responses of 24 BXD RI strains of mice and the C57BL/6J (B6) and DBA/2J(D2) progenitor strains will be characterized and quantitative trait locus (QTL) analysis and genetic correlations will be performed to provisionally identify markers associated with stress reactivity. These genetic data will be compared with morphine's behavioral effects, morphine consumption, and corticosterone responses to saline injections that already have been collected in laboratories at the sponsoring institution. In Experiment 2, morphine consumption with or without stress will be examined and QTL analyses and genetic correlations will be performed. The data from Experiment 2 will be compared with the behavioral and biological data already collected. Findings from Experiments 1 and 2 will be compared to determine possible genetic links between stress reactivity and morphine consumption. This work will provide information relevant ot individual differences in vulnerability to drug abuse.